Researchers have found that the cystic fibrosis gene may have survived for hundreds of generations because it provides protection against cholera. A study found that mice carrying the cystic fibrosis gene did not suffer from the deadly diarrhea typically caused by cholera toxin. This suggests the gene was able to persist in the population by giving carriers an advantage during cholera outbreaks throughout history, allowing them to reproduce and pass on the gene more successfully than those without it.

1. October 1994 Clue to Why Cystic Fibrosis Has Survived
The cystic fibrosis gene may have survived through hundreds of human
generations because it gives protection against cholera.
Studies at the University of North Carolina School of Medicine at Chapel
Hill have found that laboratory mice carrying cystic fibrosis genes did not
suffer the deadly diarrhea that is typically caused by cholera.
This, said a researcher who conducted the study, Dr. Sherif E. Gabriel,
may explain why cystic fibrosis is one of the most common gene defects.
quot;The frequency of the CF gene has caused people to speculate for many
years why it was at such a high level,quot; Dr. Gabriel said. quot;When you have a
gene that codes for a fatal disorder, you expect the numbers in the popula-
tion to continually be decreasing. But this has not happened with CF.quot;
A report on the research is being published on Friday in the journal Sci-
ence.
A basic belief in evolutionary biology holds that genes survive over thou-
sands of generations only if they confer some advantage to the species. If
a gene confers a disadvantage, like a lethal disorder, the theory is that it
will eventually disappear from the gene pool because carriers of the gene
would not have the opportunity to reproduce as frequently as those who
did not carry the flawed gene. But the CF gene has not obeyed this rule.
About 1 in every 20 Caucasians carries a CF gene. A single copy of the
gene does not cause the disorder.
When two carriers become parents, however, their children have a 1-in-4
chance of inheriting two CF genes. This would cause cystic fibrosis, a dis-
order that until recent decades was nearly always lethal at a young age.
Cystic fibrosis kills because it prevents the normal flow of salts out of the
gut and lungs. This leads to formation of a thick mucus that can obstruct
the intestine and block breathing in the lungs.
Dr. Gabriel said the CF gene protected carriers against cholera because it
blocked the same molecular pathway used by the disease toxin to cause
diarrhea.
Cholera kills by causing a severe and unrelenting loss of fluid. Most of the
disease victims die from dehydration. Some victims can lose up to a pint of
fluid an hour from uncontrolled diarrhea.
New York Times
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2. October 1994 Clue to Why Cystic Fibrosis Has Survived
Dr. Gabriel said cholera did not have this effect on mice that carried the
CF gene.
In his study, Dr. Gabriel said, he used 60 mice divided into three groups. A
third had a normal gene complement. A third carried one CF gene, and the
final group carried both of the CF genes. The mice were then injected with
cholera toxin.
Mice with the normal gene complement died from a typical cholera diar-
rhea. But those with one CF gene suffered from a diarrhea that was only
half as severe. And mice with both CF genes did not suffer the cholera
symptom at all, Dr. Gabriel said.
Cholera has historically killed millions of humans and is currently epidemic
in parts of India and Peru. The disease is usually spread through contami-
nated food or water. Most people recover only if they get pure water, salts
and sugars to replace that lost to diarrhea.
Dr. Gabriel suggested that in the great cholera epidemics that have struck
humanity over the centuries, carriers of the CF gene would have had a
better chance of surviving than would people who had the normal gene
complement. In this way, the CF gene would have been carried forward,
from generation to generation, in sufficient numbers to remain a part of the
human gene pool.
New York Times
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